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The authors declare that they have no conflict of interests. This review was funded by the Authors' Institutions. This workshop was financially supported by the European Federation of Periodontology and by unrestricted grants from Astra, Nobel Biocare and Straumann.

Abstract

Objective

The aim was to assess the quality of reporting of experimental research in implant dentistry by a critical evaluation of study design, outcome assessments and model validation.

Material & Methods

An online search was performed using the MEDLINE. Experimental studies performed in both animals and humans were included. A&#146;stratified random sample of the included studies was extracted and used for quantitative and qualitative analyses. Modified versions of the ARRIVE guidelines were used for quality assessment.

Results

A total of 982 papers were eligible and used for quantitative analyses. A&#146;stratified random sample of 193 publications was extracted. The dog model was the most used experimental model whereas experimental studies on humans were few. Intra-oral experimental sites dominated in human, monkey, dog and mini-pig studies. Extra oral sites dominated in rabbit, rodent and goat/sheep studies. Studies on the pathogenesis and treatment of peri-implant diseases were few.

Conclusion

Different animal models, experimental protocols and methods of analysis have been used to address different areas of experimental research in implant dentistry. Standardized designs for investigations within this type of experimental research seem to be lacking. Furthermore, in many of these studies there were limitations in reporting on methodology and statistical methods.

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Introduction

Treatment with osseointegrated dental implants have shown to be a successful therapy with good predictability for incorporation (97–98%) (Berglundh et al. 2002, Pjetursson et al. 2007) and a high survival rate after 10 years of function (approximately 89%) (Pjetursson et al. 2007). Therapy with dental implants offers the possibility of a significant improvement in function and well being for edentulous patients (Albrektsson et al. 1987). The further development and improvement of dental implants and treatment techniques requires testing in experimental models before the introduction in general clinical practice.

As of today, experimental research in implant dentistry has a strong focus on providing solutions for a predictable implant therapy also for groups of patients that previously were excluded from this treatment form, i.e. patients with a compromised general health or patients with compromised implant sites. Much interest has also been paid to both the study of biological complications at dental implants, i.e. mainly peri-implant mucositis and peri-implantitis, and the treatment of these complications. Hence, three different areas within the literature of experimental research in implant dentistry may be distinguished. These are (i) studies with focus on osseointegration/healing of peri-implant tissues, (ii) studies on healing after placement of implants in compromised patients or compromised sites and (iii) studies with focus on periimplantitis/mucositis and their treatment. Depending on the research objective the researcher may choose between a variety of different surgical models, experimental techniques, outcome variables and animal models.

Data from human studies are often considered to provide the highest level of scientific evidence. Due to the heterogeneity of human samples in terms of age, general health and different site related factors, a very high number of patients are usually required to identify any differences and to obtain a sample with an adequate statistical power. In many cases such experiments are impossible to perform for ethical reasons. Ethical considerations must be made also when planning experiments using animal models. Therefore, experimental studies must be carefully designed to allow for valid outcome assessments. That was also the reason, why Kilkenny et al. (2010) presented the ARRIVE guidelines (Animal Research: Reporting In Vivo Experiments) intended as a guide when preparing or reviewing manuscripts on animal research. The objective of the present systematic review was to assess the quality of reporting of experimental research in implant dentistry by a critical evaluation of study design, outcome assessments and model validation. The term experimental research is used for experiments where the researcher manipulates one variable, and controls/randomizes the other variables. Experimental research has a control group, the subjects have been randomly assigned between the groups, and the researcher generally only tests one effect at a time. For experimental research different animal models, including the human model can be used.

Material and Methods

Focused question

What is the quality of reporting of experimental research in implant dentistry, assessed using a modification of the ARRIVE guidelines?

Search strategy

A systematic search strategy, described in Fig. 1, was used. In the initial phase of the review a literature search was performed using the PubMed database of the US National Library of Medicine (MEDLINE via PubMed) as source in the search for studies meeting the inclusion criteria. The database was searched for studies published until June 30, 2011.

“implant placement” OR “immediate implant placement” OR “early implant placement” OR “delayed implant placement” OR “integration” OR “osseointegration” OR “osteointegration” OR “healing” OR “bone healing” OR “hard tissue healing” OR “soft tissue healing” OR “alveolar ridge” OR “bone crest” OR “socket” OR “tooth socket” OR “extraction socket” OR “fresh extraction socket” OR “post-extraction socket” OR “bone regeneration” OR “guided bone regeneration” OR “bone defect” OR “bone dehiscence” OR “ridge alteration” OR “bone resorption” OR “bone modeling” OR “bone remodeling” OR “membrane” OR “graft” OR “xenogenic graft” OR “bone graft” OR “autograft” OR “allograft” OR “allogenic graft” OR “peri-implantitis” OR “mucositis” OR “treatment”

The following search terms were used for human experimental research:

“dental implant” OR “endosseous implant” OR “titanium implant”.

Limits: “Humans”, “English Word”

AND

“implant placement” OR “immediate implant placement” OR “early implant placement” OR “delayed implant placement” OR “integration” OR “osseointegration” OR “osteointegration” OR “healing” OR “bone healing” OR “hard tissue healing” OR “soft tissue healing” OR “alveolar ridge” OR “bone crest” OR “socket” OR “tooth socket” OR “extraction socket” OR “fresh extraction socket” OR “post-extraction socket” OR “bone regeneration” OR “guided bone regeneration” OR “bone defect” OR “bone dehiscence” OR “ridge alteration” OR “bone desorption” OR “bone modeling” OR “bone remodeling” OR “membrane” OR “graft” OR “xenogenic graft” OR “bone graft” OR “autograft” OR “allograft” OR “allogenic graft” OR “peri-implantitis” OR “mucositis” OR “treatment”

AND

“histology”

Limits: Humans, English, Dental journals.

Only English written human studies published into dental journals were searched.

Inclusion criteria

Publications in peer-reviewed journal written in the English language

Experimental studies on animals and humans

A research focus on oral implant therapy

Exclusion criteria

In vitro studies

Less than four animals or subjects

Studies with a research focus on orthodontic or endodontic implants

Studies with a research focus on medical implants

Case reports

Human experimental studies published in non-dental journals

The two reviewers (IA and FV), independently, screened all titles and abstracts of the publications retrieved from the electronic search against the inclusion and exclusion criteria. A Kappa analysis for the agreement between the two reviewers was performed. In a second step, for studies appearing to meet the inclusion criteria, but for which there were insufficient data in the title and abstract to make a clear decision, the full report was obtained and was again, independently, screened by the two reviewers to establish whether the study met the inclusion criteria or not. Any disagreement was resolved by discussion among the reviewers.

The papers accepted for inclusion in the review were, subsequently, divided into seven groups depending on animal (experimental) model, i.e.:

experiments in dogs

experiments in rabbits

experiments in monkeys

experiments in goats (or sheep)

experiments in pigs

experiments in rodents

experiments in humans

To have a reasonable number of papers to analyse, it was decided to extract a stratified random sample of 199 publications. Due to the limited number of human experimental studies accepted in the review, the sampling fraction was one in the human data stratum, i.e. all experimental studies in humans were included. For the studies using different animal models a proportional allocation of the sample was decided. The random selection was generated in SAS (Statistical Analysis Software, SAS Institute Inc., Cary, NC, USA).

Review methods

Using specially designed data extraction forms, the two reviewers (IA and FV) independently, extracted data regarding the quality of each paper in the final sample. Any disagreement was discussed and resolved.

The ARRIVE (Animal Research: Reporting In Vivo Experiments) guidelines (Kilkenny et al. 2010) are based on the CONSORT check list (Schultz et al. 2010) and comprise 20 items which have to be considered when reporting of experiments on animals. The guidelines were developed in consultation with scientists, statisticians, journal editors and research funders to enable comprehensive and transparent reporting of animal studies in any area of bioscience research (Kilkenny et al. 2010). To tailor the ARRIVE guidelines to the objectives of this systematic review, a modified version of the ARRIVE guidelines (Table 1) was used allowing assessments of the quality of reporting in animal studies. For the human experimental studies, a similar modification of the ARRIVE guidelines (Table 2) was used for the data extraction. In addition, using a standard protocol, the following data were collected from the selected human and animal studies:

tissue integration at different types of implant surfaces/materials,

integration in compromised patients/sites (including early or immediate loading protocols),

pathogenesis or treatment of mucositis/periimplantitis.

Table 1. Check list for quality assessment of reporting of animal research – according to a modification of the ARRIVE guidelines (Kilkenny et al. 2010)

Item

Score

Recommended information

Title

1

0. poor

1. adequate

2. good

Provides as accurate and concise a description of the content of the article as possible.

Abstract

2

0. poor

1. adequate

2. good

Provides an accurate summary of the background, research objectives, including details of the species or strain of animal used, key methods, principal findings and conclusions of the study.

Introduction

Background

3

0. poor

1. adequate

2. good

Includes sufficient scientific background to understand the motivation and context for the study, and explains the experimental approach and rationale.

Explains how and why the animal species and model being used can address the scientific objectives and, where appropriate, the study's relevance to human biology.

Objectives

4

0. poor

1. adequate

Describes clearly the objectives of the study, or specific hypotheses being tested.

Methods

Ethical statement

5

0. no

1. yes

Contains information about the ethical review permissions, relevant licenses and national or institutional guidelines for the care and use of animals, that cover the research.

Study design

6

a,b

0. no

1. yes

Provides brief details of the study design including:

a. The number of experimental and control groups.

b. Any steps taken to minimize the effects of subjective bias when allocating animals to treatment (e.g. randomization procedure) and when assessing results (e.g. if done, describe who was blinded and when).

Experimental procedures

7

a,b,c

0. no

1. yes

Provides precise details of all procedures carried out, for each experiment and each experimental group, including controls.

a. Provides details of the statistical methods used for each analysis.

b. Specifies the unit of analysis for each dataset

c. Describes methods used to assess whether the data met the assumptions of the statistical approach.

Results

Number analysed

13

0. no

1. yes

The number of subjects/units in each group included in each analysis is reported.

If any subjects or data were not included in the analysis, an explanation is provided.

Outcomes and estimation

14

0. no

1. yes

Reports the results for each analysis carried out, with a measure of precision (e.g. standard error or confidence interval).

Adverse events

15

0. no

1. yes

Adverse events in each experimental group are reported. Describes any modifications to the experimental protocols made to reduce adverse events.

Discussion

Interpretation/scientific implications

16

0. poor

1. adequate

2. good

Interprets the results, taking into account the study objectives and hypotheses, current theory and other relevant studies in the literature.

Comments on the study limitations including potential sources of bias, limitations of the model, and the imprecision associated with the results.

Generalisability/translation

17

0. no

1. yes

Comment on whether, and how, the findings of this study are likely to translate to other subject or treatments, including the relevance to human biology.

Funding

18

0. no

1. yes

Provides information of funding sources and any conflict of interest.

When making the qualitative assessments of the selected papers a score system of 0-1 (absent-present) or 0-1-2 (poor-adequate-good) (Tables 1, 2) was used to assess the quality of each item included in the modified ARRIVE checklist. The total sum of scores was calculated for each of the selected papers. The total scores could range between 0 (minimum) and 28 (maximum). Mean, (SD), Median, Minimum and Maximum scores were calculated for all selected papers. In addition, the results from the qualitative assessments were further stratified into different groups, i.e. type of experimental model, type of research focus and time-point of publication (until 1990, 1991–2000 and 2001–2011).

Results

Screening

The result of the screening procedure is described in Fig. 1. The electronic search on the PubMed database of the US National Library of Medicine resulted in 2132 retrieved papers. The manual screening of titles and abstracts of the retrieved papers resulted in 982 papers eligible for inclusion. Twenty studies were regarded as experimental studies on humans, whereas the remaining 962 studies were performed on animals. The Kappa analysis for the agreement between the two reviewers, in the manual screening, resulted in a Kappa value of 0.8345 (ASE 0.0809) and a 95% CI between 0.68 and 0.99.

Quantitative analyses

All papers were screened and grouped according to type of animal, research focus and time-point of publication. The results from the quantitative analyses are presented in Tables 3 and 4.

Table 3. The number of experimental studies on implant dentistry, meeting the inclusion criteria, grouped according to research model, research focus and intra- or extra- oral model

Topic

Dogs

Rabbits

Monkeys

Goats/sheep

Mini-pigs

Rodents

Humans

Total

Healing/tissue integration

199

157

41

41

52

66

9

565

Healing/compro-mized sites

190

50

16

8

16

64

9

353

Study/treatment of mucositis/peri-implantitis

49

0

13

0

0

0

2

64

Total

438

207

70

49

68

130

20

982

Intra-oral model

417

4

69

14

52

19

20

595

Extra oral model

21

203

1

35

16

111

0

387

Table 4. The number of experimental studies on implant dentistry, meeting the inclusion criteria, grouped according to research focus and publication period

Research focus

Healing/tissue integration

Healing/compro-mized sites

Study/treatment of mucositis/peri-implantitis

Total

–1990

25

5

0

30

1991–2000

146

100

29

275

2001–2011

394

248

35

677

Total

565

353

64

982

Animal models

0f all included publications, 438 papers used the canine model as experimental model of research, 207 papers used the rabbit model, 70 papers used the monkey model, 49 papers used the goat model, 68 papers used the mini-pig model and 130 papers used rodents as experimental animals (Table 3).

Dog studies

A total of 199 papers investigated on the healing and tissue integration of implants. Thirteen (6.5%) of these papers used an extra-oral experimental model. A total of 190 papers investigated on the healing of implants into compromised sites/subjects; 8 (4.2%) of these papers utilized an extra-oral experimental model. Forty-nine papers evaluated the study/treatment of mucositis/periimplantitis. None of these studies utilized the extra-oral model.

Rabbit studies

A total of 157 papers investigated on the healing and tissue integration of implants. A total of 156 (99.4%) of these papers used an extra-oral experimental model. Fifty papers investigated on the healing of implants into compromised sites/subjects; 47 (94%) of these papers utilized an extra-oral experimental model. No papers evaluating the study/treatment of mucositis/periimplantitis were found.

Monkey studies

Forty-one papers investigated on the healing and tissue integration of implants. Sixteen papers investigated on the healing of implants into compromised sites/subjects and 13 papers evaluated the study/treatment of mucositis/periimplantitis. All studies but one, performed in the monkey model utilized intraoral sites.

Goat/sheep studies

Forty-one papers investigated on the healing and tissue integration of implants. 33 (80.5%) of these papers used an extra-oral experimental model. Eight papers investigated on the healing of implants into compromised sites/subjects; 2 (25%) of these papers utilized an extra-oral experimental model. No papers evaluating the study/treatment of mucositis/periimplantitis were found.

Mini-pig studies

Fifty-two papers investigated on the healing and tissue integration of implants. Fourteen (26.9%) of these papers used an extra-oral experimental model. Sixteen papers investigated on the healing of implants into compromised sites/subjects; 2 (12.5%) of these papers utilized an extra-oral experimental model. No papers evaluating the study/treatment of mucositis/periimplantitis were found.

Rodent studies

Sixty-six papers investigated on the healing and tissue integration of implants. Fifty-seven (86.4%) of these papers used an extra-oral experimental model. Sixty-four papers investigated on the healing of implants into compromised sites/subjects; 54 (84.4%) of these papers utilized an extra-oral experimental model. No papers evaluating the study/treatment of mucositis/periimplantitis were found.

Experimental research on humans

The search resulted in 187 retrieved papers. After an initial phase of title and abstract screening 20 potentially relevant articles were identified.

Nine papers investigated the healing and tissue integration of implants. Nine papers investigated on the healing of implants into compromised sites/subjects; two papers evaluated the study/treatment of mucositis/periimplantitis. All of the papers with experimental research on humans utilized an intra-oral experimental model.

Time-point for publication

Thirty studies of all studies meeting the inclusion criteria (982) were published before 1991. A total of 275 studies were published during the years 1991 until 2000, while the majority of studies, i.e. 677, were published after the year 2000. The distribution between the three different research foci were similar in the two later age cohorts, whereas in the cohort before 1991 studies with a focus on healing/integration dominated and no studies on pathogenesis or treatment of peri-implant diseases were found. (Table 4)

Stratified random sample

The stratified random sample of all studies consisted of 199 publications. After reviewing the full text articles another six papers were excluded. Two papers were case reports, two papers were short communications, one paper was a review and one paper was excluded because of too low number of experimental animals (Fig. 1). The final sample is presented in Table 5a–g and described according to animal model and research focus in Table 6.

Table 6. The number of experimental studies on implant dentistry, in the stratified random sample, grouped according to research model, research focus and intra- or extra- oral model

Topic

Dogs

Rabbits

Monkeys

Goats/sheep

Mini-pigs

Rodents

Humans

Total

Healing/tissue integration

42

32

5

8

14

15

7

123

Healing/compro-mized sites

33

6

3

0

0

9

9

60

Study/treatment of mucositis/peri-implantitis

3

0

4

0

0

0

3

10

Total

78

38

12

8

14

24

19

193

Intra-oral model

71

1

11

2

7

6

19

117

Extra oral model

7

37

1

6

7

18

0

76

Study design, outcome assessments and model validation

The vast majority of the dog, monkey and human studies used intra-oral research models. The mini-pig studies were evenly distributed between studies using intra- or extra-oral experimental sites, whereas the majority of rabbit, goat/sheep and rodent studies used extra oral experimental sites.

A wide heterogeneity was found regarding (i) the number of animals included in each study, (ii) the number of test groups (different healing times or treatments) and (iii) the number and type of outcome variables chosen for evaluation. A wide heterogeneity was also observed regarding histological processing such as different methods for tissue preservation, embedding and cutting methods and also with regard to the type of microscopical technique, (e.g. light microscopy, fluorescence microscopy or electron microscopy).

Although the main outcome variables reported in the studies included in the stratified random sample were different types of qualitative and quantitative histological assessments, clinical, surgical,radiographical, microbiological and bio-mechanical assessments were also made.

Histology was a common method of analysis in all animal models, whereas microbiological techniques were used mainly in monkeys and bio-mechanical tests were most common in rabbit studies.

Dog studies

A total of 78 dog studies were included in the stratified random sample. Seventy-one studies used the intra-oral research model to investigate on (i) healing/tissue integration (35 studies), (ii) healing of compromised sites/subjects (33 studies) and (iii) study/treatment of mucositis/peri-implantitis. Seven studies used the extra oral model to investigate on healing/tissue integration. The number of animals included in each dog study varied and up to 36 animals were included. In 58 of 78 studies ≤ 8 animals were included. Most of the studies included a number of treatment groups with different healing times that varied from 0 to 12 months. It was therefore, difficult to identify the real n for the statistical analysis. In ambition to test for many different variables in each experiment a general trend was that the n was low. Histological methods were used in 72 of 78 studies. Other methods used for assessing the outcome variables were micro-CT (3 studies), conventional radiographs (16 studies), biomechanical testing (10 studies) surgical and clinical examinations (6 studies) and laser Doppler (1 study).

Rabbit studies

A total of 38 rabbit studies were included in the stratified random sample. Thirty-seven studies used the extra oral research model to investigate (i) healing/tissue integration (31 studies), (ii) healing of compromised sites/subjects (six studies), whereas no studies were encountered on research focus 3. One study used the intra-oral experimental model to investigate on healing/tissue integration. The number of animals included in the rabbit studies varied and up to 48 animals were included. Most of the studies included a number of treatment groups with different healing times that ranged between 1 week and 12 months. Histological methods were used in 30 of 38 studies. Other methods used for assessing the outcome variables were micro-CT (2 studies), conventional radiographs (1 study), biomechanical testing (21 studies) and clinical examinations (1 study).

Monkey studies

Twelve monkey studies were included in the stratified random sample. Eleven studies used the intra-oral research model to investigate on (i) healing tissue/integration (four studies), (ii) healing of compromised sites/subjects (three studies) and (iii) study/treatment of mucositis/peri-implantitis (four studies). One study used the extra oral experimental model to investigate on healing/tissue integration. The number of animals included varied and up to 18 animals were included. Healing times ranged between 4 weeks and 18 months. Histological methods were used in 8 of 12 studies. Microbiological samples of submucosal plaque for phase contrast microscopic analysis were obtained in two studies. Other methods used for assessing the outcome variables were conventional radiographs (five studies), biomechanical testing (one study) and clinical/surgical examinations (four studies).

Goat/sheep studies

Eight goat/sheep studies were included in the stratified random sample. All but two studies used the extra oral research model to investigate on healing and tissue integration. The number of animals included varied between 3 and 12 animals. Healing times ranged between 1 h and 3 months. Histological methods were used in all studies and biomechanical testing was included in two studies. No other methods were used in this animal model.

Minipig studies

A total of 14 minipig studies were included in the stratified random sample. Fifty percentage of the studies used the extra oral research model to investigate on healing and tissue integration. The number of animals included varied between 3 and 12 animals. Healing times ranged between 1 h and 3 months. Histological methods were used in all studies and biomechanical tests were included in two studies. No other methods were used for evaluations in this animal model.

Rodent studies

A total of 24 studies were included in the stratified random sample. Eighteen studies used the extra oral research model to investigate on (i) healing/tissue integration (10 studies), (ii) healing of compromised subjects (eight studies) whereas no study on study/treatment of mucositis/peri-implantitis was encountered. Six studies used the intra-oral model to investigate on (i) healing/tissue integration (five studies) and (ii) healing of compromised subjects (one study). The number of animals included in the rodent studies varied and up to 152 animals were included. Healing times varied between 1 week and 12 months. Histological methods were used in all the presented studies. Other methods used for assessing the outcome variables were biomechanical testing (five studies), micro-CT (two studies) and conventional radiographs (two studies).

Human studies

A total of 19 studies were included in the stratified random sample. All studies used the intra-oral research model to investigate on (i) healing/tissue integration (eight studies), (ii) healing of compromised sites/subjects (nine studies) and (iii) study on study/treatment of mucositis/peri-implantitis (two studies). The number of subjects included in the human experiments varied between 4 and 48 included subjects. Follow-up times ranged between 7 days and 12 months. Histological methods were used in all the presented studies. Other methods used for assessing the outcome variables were biomechanical testing (one study), conventional radiographs (one study) and measurement of clinical variables (two studies).

Qualitative assessment

The results from the qualitative assessments of the stratified sample (193) are reported in Table 7 and Fig. 2. The mean score achieved by all the selected papers was 18.33. The score for the different animal models ranged between 16.08 for the experimental studies in monkeys and 19.35 for the experimental studies in dogs. The score depending on the grouping of research focus varied between 17.93 and 19.40 for the Focus 1 (Healing) and Focus 2 (Healing of compromised sites/subjects) studies, respectively. The studies published before 1991 reached the lowest mean score i.e. 13.75, whereas the studies published between 1991 and 2000 and between 2001 and 2011 reached scores amounting to 16.9 and 19.2 respectively.

Figure 2.

Histograms presenting the frequency distribution (%) of the scores assessed for each item of the modified ARRIVE guidelines (Tables 2 and 3). Items 1–3 and 16 scored 0, 1 or 2 (poor, adequate or good). All other items scored 0 or 1 (yes or no). The data are presented for all included studies.

Table 7. Results from the qualitative assessments of the stratified sample of selected papers (193) divided and grouped according to type of animal model, research focus and publication period. Scores according to the modified ARRIVE guidelines (Tables 2, 3)

Group

Mean

Median

SD

Min

Max

All studies

18.33

19

3.75

7

27

Before 1991

13.75

14

2.98

10

17

1991–2000

16.9

17

4.13

7

25

2001–2011

19.2

20

3.21

11

27

Dog

19.35

20

3.78

7

27

Rabbit

16.6

17

3.8

8

24

Monkey

16.08

17

4.69

8

22

Goat

19.14

20

3.57

12

23

Minipig

17.78

19

3.06

10

20

Rodents

18

18

2.75

11

23

Humans

19.2

19

2.58

16

24

Extraoral

17.52

18

3.70

8

24

Intraoral

18.91

19

3.66

7

27

Focus 1

17.93

19

3.68

8

25

Focus 2

19.4

20

3.56

10

27

Focus 3

18

20

5.24

7

22

The frequency distribution of the scores, item by item, according to the modification of the ARRIVE guidelines (Tables 2, 3) was assessed and is presented for all studies (Fig. 2) and for the different subgroups, separately (Table 8). Four items of the checklist were scored 0, 1 or 2 (poor, adequate or good) whereas all other items were scored 0 or 1 (yes or no).

Table 8. Table presenting the frequency distribution of the scores assessed for each item of the modified ARRIVE guidelines (Tables 2 and 3). Items 1–3 and 16 scored 0, 1 or 2 (poor, adequate or good). All other items scored 0 or 1 (yes or no). The data are presented for all included studies and for different study subgroups and research foci (RF)

Arrive

Score

Dogs

Rabbits

Monkeys

Goats/sheep

Minipigs

Rodents

Humans

All studies (%)

RF 1

RF 2

RF 3

1

0

4

3

0

1

0

1

0

9 (4.66)

8

1

0

1

49

31

8

5

11

14

11

129 (66.8)

82

40

7

2

25

4

4

2

3

9

8

55 (28.4)

33

19

3

2

0

6

10

2

0

1

1

0

20 (10.3)

15

5

0

1

59

25

9

6

11

17

16

143 (74)

89

46

8

2

13

3

1

2

2

6

3

30 (15.5)

19

9

2

3

0

3

9

3

0

2

0

0

17 (8.8)

12

3

2

1

47

27

9

5

8

20

14

130 (67.3)

85

38

7

2

28

2

0

3

4

4

5

46 (23.3)

26

19

1

4

0

2

0

0

0

1

1

0

4 (2)

3

0

1

1

76

38

12

8

13

23

19

189 (98)

120

60

9

5

0

28

20

7

4

4

11

8

82 (42.4)

58

21

3

1

50

18

5

4

10

13

11

111 (57.6)

65

39

7

6a

0

5

2

1

0

0

2

1

11 (5.6)

6

5

0

1

73

36

11

8

14

22

18

182 (94.4)

117

55

10

6b

0

35

25

9

2

11

17

10

109 (56.4)

79

25

5

1

43

13

3

6

3

7

9

84 (43.6)

44

35

5

7a

0

4

1

1

1

0

0

1

8 (4.1)

5

2

1

1

74

37

11

7

14

24

18

185 (95.9)

118

58

9

7b

0

6

2

5

1

1

0

0

15 (7.7)

12

1

2

1

72

36

7

7

13

24

19

178 (92.3)

111

59

8

7c

0

2

0

0

1

1

1

1

6 (3.1)

4

1

1

1

76

38

12

7

13

23

18

187 (96.9)

119

59

9

8

0

23

6

2

1

4

3

6

45 (23.3)

34

9

2

1

55

32

10

7

10

21

13

148 (76.7)

89

51

8

9

0

53

25

8

1

13

11

14

125 (64.7)

85

35

5

1

25

13

4

7

1

13

5

68 (35.3)

38

25

5

10a

0

1

5

0

0

14

3

0

23 (11.9)

9

12

2

1

77

33

12

8

0

21

19

170 (98.1)

114

48

8

10b

0

76

38

12

7

13

24

19

189 (98)

119

60

2

1

2

0

0

1

1

0

0

4 (2)

4

0

0

11

0

7

3

3

1

1

4

0

19 (9.8)

12

6

1

1

71

35

9

7

13

20

19

174 (90.2)

111

24

9

12a

0

14

7

6

2

3

8

5

45 (23.3)

27

16

2

1

64

31

6

6

11

16

14

148 (76.7)

96

44

8

12b

0

41

24

9

4

8

20

13

119 (61.6)

73

39

7

1

37

14

3

4

6

4

6

74 (38.4)

50

1

3

12c

0

57

29

9

2

13

17

17

144 (74.6)

99

40

5

1

21

9

3

6

1

7

2

49 (25.4)

24

20

5

13

0

24

24

5

2

4

16

1

76 (39.3)

53

19

4

1

54

14

7

6

10

8

18

117 (60.7)

70

41

6

14

0

7

2

0

1

4

4

0

18 (9.3)

13

4

1

1

71

36

12

7

10

20

19

175 (90.7)

110

55

9

15

0

16

24

6

1

7

13

4

71 (36.7)

47

19

5

1

62

14

6

7

7

11

15

122 (63.3)

76

41

5

16

0

6

3

6

1

1

0

0

17 (8.8)

10

5

2

1

43

30

5

5

11

16

10

120 (62.1)

80

35

5

2

29

5

1

2

2

8

9

56 (29.1)

33

20

3

17

0

13

16

2

2

2

9

0

44 (22.7)

38

4

2

1

65

22

10

6

12

15

19

149 (77.3)

85

56

8

18

0

20

15

4

1

4

5

11

60 (31)

36

21

3

1

58

23

8

7

10

19

8

133 (69)

87

39

7

For the ARRIVE items 5, 6b, 9, 10b, 12b and 12c, more than 40% of the studies scored 0. Hence, 42.7% of the studies did not contain any information on ethical considerations, 56.25% of the studies did not present information regarding randomization or blinding procedures, 66.66% of the studies did not report any information of housing and husbandry conditions (animal studies) or provided details of the dental history of the patients (human studies). 97.91% of the studies failed to report on any sample size calculation. 61.97% of the studies did not specify the unit of analysis used for the statistical assessment and 76.56% of the studies did not provide details of or discuss the validation of the statistical method used. No major differences regarding the score distribution of these items were observed between the different experimental models or research foci (Table 8).

Discussion

In this systematic review the quality of reporting of experimental research was investigated. In addition, aspects on study design, outcome assessments and model validation are provided.

Due to the huge amount of experimental studies meeting our inclusion criteria, found in the systematic search, using the PubMed database of the US National Library of Medicine (MEDLINE via Pubmed), a stratified random representative sample was extracted and used for the analysis. A quantitative as well as a qualitative analysis was performed.

The quantitative analysis was based on 982 publications reporting of experimental research within the field of implant dentistry. The data extracted from this pool of studies revealed that experiments on the study and treatment of mucositis/peri-implantitis were few. These studies were performed in dogs (49 studies), monkeys (13 studies) or humans (2 studies). The choice of animal model probably reflects a limitation for the other animal models for this type of research. Studies with a research focus on healing in compromised subjects or sites were performed in all animal models included in this review. The majority of these were dog studies, manly focused on healing in compromised sites, while many of the rabbit and rodent studies focused on healing in systemically compromised subjects. For the study of healing and tissue integration of implants, all animal models included in this review have been used. The proportion of studies, within each animal model used for this research focus, however, varies. 45.4% of the dog studies, 75.8% of the rabbit studies, 58.5% of the monkey studies, 60.2% of the goat studies, 76.4% of the minipig studies and 50.7% of the rodent studies were used for the study of healing and tissue integration of implants. Furthermore, it has to be taken into consideration that most of rabbit, rodent and goat studies used extra oral surgical models. Common outcome assessments associated with the extra oral model, were, beside histology, different methods for mechanical testing of implant retention or stability, such as removal torque tests, push out or push in tests. Anatomical and morphological differences between extra and intra-oral models and the type of analysis related to these models makes the interpretation of the results, difficult. The extrapolation of such results into clinical settings are, therefore, often not possible or should be interpreted with caution.

The qualitative analysis was based on data extraction from 193 publications reporting of experimental research within the field of implant dentistry. The data extracted were chosen mainly according to the ARRIVE guidelines. In our systematic review we selected 24 items from the ARRIVE guidelines and added another seven items for our qualitative analysis. It should however be kept in mind that the items from the ARRIVE guidelines are not intended as quality descriptors of a manuscript. Instead the intention is to use them as a checklist or guideline when reporting from experimental research. For our review, we modified the original ARRIVE guidelines (Kilkenny et al. 2010) to be more suited for quality assessments. Despite the modification and depending on the type of study that is analysed, all items are not always appropriate to include and they may not have an equal quality value compared to other items. One example of this may be that when assessing the items regarding statistics, a frequent finding was that although the n number was reported, it was not properly calculated or it was very low due to a study design with many different experimental groups.

Although a trend towards higher mean ARRIVE scores was observed for more recent studies, the results from the qualitative analysis revealed that the main shortcomings when reporting of experimental research in implant dentistry were related to basic aspects of methodology. Limited information was provided on randomization and blinding procedures, as well as statistical methods. This was a general finding, which was observed in all studies of the stratified random sample as well as within the different animal models and research foci. Indeed, between 56% and 98% of the studies did not present information regarding randomization or blinding procedures, sample size calculations, did not specify the unit of analysis used for the statistical assessment or provide details of or discuss the validation of the statistical method used. The lack of such critical information needs to be considered when analyzing data from experimental research and points out critical issues that must be addressed in the future. This is in agreement with a recently published systematic review (Faggion et al. 2011). In this review the risk of bias of animal studies on regenerative procedures was analysed and it was concluded that methodological aspects of animal experiments in periodontology and implantology should be improved in order to reduce such risks.

Data from human studies are often considered as the highest level of scientific evidence. Despite this general opinion, human experimental studies in implant dentistry are few. The reasons for this may be many; the heterogeneity of human samples in terms of age, general health and different site related factors often make comparisons, conclusions and reaching adequate statistical power difficult unless a very high number of subjects are recruited. In many cases such experiments are also difficult to perform for ethical reasons since histological samples are often required.

The main findings in this systematic review were:

The dog model was the commonly most used experimental model (44.6%) followed by the rabbit model (21.1%).

Studies on healing and tissue integration of dental implants was the most investigated research focus, representing 57.5% of all experimental research in implant dentistry. This focus was followed by research on healing of compromised sites or systematically compromised subjects (35.9%).

Experimental studies on the pathogenesis and treatment of peri-implant diseases were few and made up 6.4% of all experimental research within implant dentistry.

All animal models included in this review were used for research focus 1 and 2, whereas only dogs, monkeys and humans were used for research focus 3.

The dog was the most utilized animal model for investigations on healing of compromised sites, whereas rodents were mainly used in studies on healing of systematically compromised subjects.

Both intra- and extra- oral surgical models have been used for research on healing and tissue integration.

Intra-oral surgical models dominated in experiments on the healing of compromised sites and the study or treatment of mucositis or peri-implantitis, whereas extra-oral models dominated in experiments on healing of systematically compromised subjects.

The mean score in the qualitative analysis of the stratified sample (193) achieved by all the selected papers was 18.33.

The score for the different animal models ranged between 16.1 for the experimental studies in monkeys and 19.4 for the experimental studies in dogs.

Studies published before 1991 reached the lowest mean score i.e. 13.8, while the studies published between 1991 and 2000 and between 2001 and 2011 reached scores amounting to 16.9 and 19.2, respectively.

Between 56% and 98% of the studies did not present information regarding randomization or blinding procedures, or provided sufficient information about the statistical methods used.

In conclusion, a wide range of animal models, experimental protocols (intraoral/extra-oral) as well as methods of analysis has been used to address different areas of experimental research in implant dentistry. In a high number of these studies there were limitations in reporting on methodology, mainly regarding randomization/blinding procedures as well as statistical methods. Hence, results and conclusions should be interpreted in relation with the limitations inherent in the methodology and specific animal model used.

Clokie, C. M. & Warshawsky, H. (1995) Morphologic and radioautographic studies of bone formation in relation to titanium implants using the rat tibia as a model. International Journal of Oral and Maxillofacial Implants10, 155–165.

14Øystein Fardal, Jostein Grytten, A comparison of teeth and implants during maintenance therapy in terms of the number of disease-free years and costs - an in vivo internal control study, Journal of Clinical Periodontology, 2013, 40, 6, 645Wiley Online Library